Gene networks derived from WGCNA hub genes similarly revealed genes related to inflammatory processes as strongly connected network nodes. Here, STAT3 represents a conserved network hub node in all three brain regions. STAT3 is a member of the JAK/STAT pathway and acts as a transcription factor upon activation by cytokines, hormones and growth factors [50]. Interestingly, a recent study assessing expression signatures of alcohol withdrawal in rats discovered a very similar gene network in the hippocampus with STAT3 as a hub node surrounded by a network of downstream targets [51]. The authors also discovered increased levels of STAT3 and its neuroinflammation-related target genes in postmortem brain tissue of subjects with AUD. Activation of the STAT3 gene network was found to be primarily restricted to astrocytes. This supports the results of the cell type enrichment analyses, where enrichment of astrocytic expression signatures was detected for upregulated DE genes in the CN.
